Oesophageal adenocarcinoma is increasing rapidly in western countries [1, 2] and patients usually present late with locally advanced disease leading to a dismal overall 5 year survival rate of 13% [3]. Barrett's oesophagus (BE), as defined by intestinal metaplasia, is the major identified risk factor for this cancer [4] and in those patients with oesophageal adenocarcinoma at presentation 90% have evidence of BE following shrinkage of the tumor post-chemotherapy [5]. However, because the majority (86%) of adenocarcinomas present de novo [6] (without prior diagnosis of BE) it is likely that a large number of BE patients remain undiagnosed in the population. This idea is supported by the high prevalence of BE (7-25% for segments of any length and 0.7-7% for long segment Barrett's) in asymptomatic patients who agreed to have a screening upper GI endoscopy when attending for colonoscopy in the US [7-9]. In keeping with these overall figures the prevalence of BE of any length was reported to be between 1 and 8% in all corners to endoscopy (reviewed in Pera, 2003 [10]). The only population prevalence data available suggests that BE is present in 1.6% of the general Swedish population [11].
Evidence from non-randomized retrospective studies demonstrated an improvement in 5-year actuarial survival from 13-43% to 62-100% in patients with surveillance-detected oesophageal adenocarcinomas [12-18]. These data suggest a potential benefit for early detection although lead time bias needs to be accounted for. Rapid advances in endoscopic technologies (reviewed by Reddymasu and Sharma [19]) as well as the development of chemoprevention strategies [20, 21] afford the opportunity to improve patients' outcomes if disease is detected early.
Thus, identification of undiagnosed BE patients should ultimately reduce mortality from oesophageal adenocarcinoma. To attain this objective, population-based screening for Barrett's is required. However there are major feasibility and cost implications for the wide-scale application of screening using the gold standard endoscopy [22].
Since the architecture of the tissue is well conserved, H&E slides may be reviewed by an expert gastrointestinal histopathologist but morphology alone is often not sufficient to diagnose BE and is open to subjectivity.
Novel screening strategies might include symptom nomograms, wireless capsule endoscopy and balloon cytology [23-25] but these have not yet been demonstrated to be sufficiently sensitive and specific for clinical use [26-28]. Recently, a study using a wireless video capsule attached to a string, allowed a more careful examination of the oesophagus and eliminated previous a major imaging drawback of fast oesophageal transit time with a reported sensitivity of 93.5% [29]. However, this approach does not permit a pathological diagnosis or the potential for implementing risk stratification using biomarkers.
Neither the British Society of Gastroenterology nor the American Gastroenterology Association currently recommend endoscopic screening for BE [22, 57] (recommendations grade C and B respectively, both based on cohort and case control studies). However, both professional organizations agree that surveillance is in order once BE is diagnosed. However, for surveillance to be of use, all Barrett's patients, symptomatic or asymptomatic would need to be diagnosed. This suggests population screening for BE may be recommended if a cost effective test could be developed. It is a problem that there is currently no suitable cost effective test available. The present invention seeks to overcome problem(s) in the art.